Hydrazine hydrate (1:1) → (2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide

HRID 454999Notes

Reaction equation

HRID 454999 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][C@H:13]([NH:26][C:27]([C@H:29]1C[C@@H:30]1C1SC=CC=1)=[O:28])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]([CH3:25])[CH2:23][CH3:24])=[CH:16][CH:15]=1.O.NN>C(O)C>[NH2:3][CH2:12][C@H:13]([NH:26][C:27](=[O:28])[C@H:29]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:30])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]([CH3:25])[CH2:23][CH3:24])=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67430811(1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic acid {(R)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-1-[4-((S)-2-methyl-butoxy)-phenyl]-ethyl}-amide

Product 1

HCID 51354470(2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamideYield 102.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic acid {(R)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-1-[4-((S)-2-methyl-butoxy)-phenyl]-ethyl}-amide (330 mg, 0.66 mmol) and ethanol (20 mL) was treated dropwise with hydrazine monohydrate (0.32 mL, 6.6 mmol), and the resulting reaction was maintained at 60° C. overnight. The mixture was allowed to cool to room temperature and the solids were removed by filtration. The filtrate was concentrated to dryness, and triturated with ethyl acetate (15 mL), and the mixture was filtered. The collected solids were air dried, then dissolved in diethyl ether (5 mL). The resulting solution was treated with concentrated HCl (0.1 mL), and the precipitate was collected by filtration to afford (2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide (120 mg, 52% yield) as a white solid: 1H NMR (400 MHz, MeOD) δ 7.33 (d, J=8.6 Hz, 2H), 7.16 (dd, J=5.1, 1.3 Hz, 1H), 6.98 (d, J=8.6 Hz, 2 H), 6.89 (dd, J=5.1, 3.5 Hz, 1H), 6.85 (d, J=3.3 Hz, 1H), 5.17 (dd, J=8.7, 5.9 Hz, 1H), 3.86 (dd, J=9.1, 5.8 Hz, 1H), 3.79 (dd, J=9.1, 6.3 Hz, 1H), 3.27-3.31 (m, 2H), 2.57 (ddd, J=9.3, 5.7, 4.2 Hz, 1H), 2.00 (ddd, J=8.3, 5.2, 4.2 Hz, 1H), 1.85 (dq, J=13.1, 6.6 Hz, 1H), 1.55-1.64 (m, 2H), 1.25-1.34 (m, 2H), 1.03 (d, J=6.8 Hz, 3 H), 0.97 (t, J=7.5 Hz, 3H); LRMS (ESI) m/e 373.1 [(M+H)+, calcd for C21H29N2O2S 373.2].

Workup

  1. customthe resulting reaction
  2. temperatureto cool to room temperature
  3. customthe solids were removed by filtration
  4. concentrationThe filtrate was concentrated to dryness
  5. customtriturated with ethyl acetate (15 mL)
  6. filtrationthe mixture was filtered
  7. customdried
  8. dissolutiondissolved in diethyl ether (5 mL)
  9. additionThe resulting solution was treated with concentrated HCl (0.1 mL)
  10. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-97eb194a06dc4e1ba93f3afb9a188284
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Reaction notes

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